Sir Jeremy Heywood, former cabinet secretary and head of the civil service, has died aged 56.
In a statement, his wife Suzanne said he died on Sunday morning.
Sir Jeremy retired from his posts last month, having been diagnosed with cancer last year.
He worked under prime ministers Tony Blair, Gordon Brown, David Cameron and Theresa May during his career in the civil service.
His wife described Sir Jeremy as a wonderful father who crammed a huge amount into his 56 years.
She said: He saw it as a huge privilege to work so closely with four prime ministers and two chancellors and was unwavering in his efforts to help each of them reach their goals.
He was always conscious of the need for civil servants to see the world through ministers eyes while at the same time respecting the boundaries between politicians and civil servants.
Away from his work, he inspired admiration, respect and affection in his many and diverse group of friends and returned it to them.
Jeremy could light up any room or conversation and loved hosting a good party.
Mrs May said Sir Jeremy worked tirelessly to serve our country and said his death was a huge loss to British public life.
The prime minister said: This is extremely sad news and all of my thoughts are with Jeremys family and friends.
The many retirement tributes paid to Jeremy from across the political spectrum in recent weeks demonstrated his extraordinary talent supporting and advising prime ministers and ministers, and leading the civil service with distinction.
He worked tirelessly to serve our country in the finest traditions of the civil service and he is a huge loss to British public life.
I will always be grateful for the support which he gave me personally and will remember his achievements across his career as we regret that he did not have the chance to offer his talents for longer in retirement.
Jeremy will be sorely missed and I send my deepest condolences to Suzanne and the children and to all his family and many friends.